Spatial transcriptomics of fixed tissue micro-regions using Pick-Seq [tonsil]

Spatial transcriptomics and multiplexed imaging are complementary methods for studying tissue biology. Here we describe a simple method for transcriptional profiling of formalin fixed histology specimens based on mechanical isolation of tissue micro-regions containing 5-20 cells. Sequencing micro-regions from an archival melanoma specimen having multiple distinct histologies reveals significant differences in transcriptional programs associated with tumor invasion, proliferation, and immunoediting and parallel imaging confirms changes in immuno-phenotypes and cancer cell states. mRNA from 40μm regions of interest were collected from two histological sites in human FFPE tonsil sections, sequenced and gene expression profiles were analyzed.